Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the gp41 C-terminal tail of human immunodeficiency virus type 1.

The possibility that epitopes from the C-terminal tail of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) are exposed the surface of the virion has long been contentious. Resolution of this has been hampered by the absence of any neutralizing monoclonal antibodies, but we have recently epitope-purified a neutralizing polyclonal IgG specific for one of the putative gp41 tail epitopes, (746)ERDRD(750). This was obtained from mice immunized parenterally with a plant virus chimera expressing residues 731-752 from the gp41 tail. The ERDRD epitope is highly conformational and is conserved in 81% of B clade viruses. Here, it is shown that this polyclonal ERDRD-specific IgG is highly potent, with an affinity of 2.2x10(8) M(-1), and a neutralization rate constant (-K(neut)) of 7.8x10(4) M(-1) s(-1) that exceeds that of nearly all other known HIV-1-neutralizing antibodies. ERDRD-specific IgG gave 50% neutralization at 0.1-0.2 microg/ml and 90% neutralization at approximately 3 microg/ml. It also neutralized virus that was already attached to target cells, and this and other data suggest that it neutralized by inhibiting a virion event that precedes the fusion-entry process. Consistent with this conclusion was the finding that neutralizing amounts of ERDRD-specific IgG did not inhibit the attachment of free virus to target cells. ERDRD-specific IgG was also cross-reactive and neutralized all but one of six B clade T cell line-adapted strains tested.